title: Tunable elastin-like polypeptide hollow sphere as a high payload and controlled delivery gene depot.
abstract: Self-assembly driven processes can be utilized to produce a variety of nanostructures useful for various in vitro and in vivo applications. Characteristics such as size, stability, biocompatibility, high therapeutic loading and controlled delivery of these nanostructures are particularly crucial in relation to in vivo applications. In this study, we report the fabrication of tunable monodispersed elastin-like polypeptide (ELP) hollow spheres of 100, 300, 500 and 1000 nm by exploiting the self-assembly property and net positive charge of ELP. The microbial transglutaminase (mTGase) cross-linking provided robustness and stability to the hollow spheres while maintaining surface functional groups for further modifications. The resulting hollow spheres showed a higher loading efficiency of plasmid DNA (pDNA) by using polyplex (~70 μg pDNA/mg of hollow sphere) than that of self-assembled ELP particles and demonstrated controlled release triggered by protease and elastase. Moreover, polyplex-loaded hollow spheres showed better cell viability than polyplex alone and yielded higher luciferase expression by providing protection against endosomal degradation. Overall, the monodispersed, tunable hollow spheres with a capability of post-functionalization can provide an exciting new opportunity for use in a range of therapeutic and diagnostic applications.
authors.affiliation: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway, Newcastle Road, Dangan, Galway.
authors.forename: Biraja C
authors.initials: BC
authors.lastname: Dash
authors.forename: Sunil
authors.initials: S
authors.lastname: Mahor
authors.forename: Oliver
authors.initials: O
authors.lastname: Carroll
authors.forename: Asha
authors.initials: A
authors.lastname: Mathew
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Woodhouse
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001682:Biological Availability; D002470:Cell Survival; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D004549:Elastin / Q000235:genetics*; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005663:Furans / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D053769:Nanocapsules / Q000737:chemistry*; D010196:Pancreatic Elastase / Q000378:metabolism; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000737:chemistry; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013499:Surface Properties; D014162:Transfection; D011503:Transglutaminases / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D005663:Furans; D053769:Nanocapsules; D010446:Peptide Fragments; D011109:Polymethacrylic Acids; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; C018674:tetrahydrofuran; D004549:Elastin; D011503:Transglutaminases; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase